The objective of this application is to define the leadership and operational structures for the Microbicide Trials Network (MTN). The MTN was first established in 2006 to identify a safe and effective microbicide for HIV prevention. From the outset, the MTN targeted key populations at risk of HIV including women in Sub- Saharan Africa, adolescents, pregnant and lactating women, and MSM. Over the last six years, the MTN has developed an expansive program in vaginal and rectal microbicide development, with unique and substantial contributions to the field in the understanding of the safety, effectiveness, pharmacokinetics, and the behavioral context associated with the use of topical microbicides. Since its inception, it has developed a total of 31 new protocols. The proposed plan in this continuing application is to build on this foundation of research to expand the portfolio of active agents to be tested in phase 1-3 studies over the next 7 years. It is anticipated that these studies will build toward a phase 2B/3 studies of a rectal microbicide and a combination antiretroviral/hormonal contraceptive ring. Cutting edge biomedical and behavioral research approaches will be incorporated through the contributions of the biomedical and behavioral research working groups, and community perspectives on protocols will be incorporated through the community working group.